首页|The evolving roles of Wnt signaling in stem cell proliferation and differentiation,the development of human diseases,and therapeutic opportunities

The evolving roles of Wnt signaling in stem cell proliferation and differentiation,the development of human diseases,and therapeutic opportunities

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The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across species.Wnt proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling pathways.Cellular behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling paths.Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues.This includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem cells.Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties.Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders.Not surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including cancer.Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and metastasis.Altogether,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway.Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

β-CateninCancerCanonical WntDiseaseNon-canonical WntStem cellsTargeted therapyWnt signaling

Michael Yu、Kevin Qin、Jiaming Fan、Guozhi Zhao、Piao Zhao、Wei Zeng、Connie Chen、Annie Wang、Yonghui Wang、Jiamin Zhong、Yi Zhu、William Wagstaff、Rex C.Haydon、Hue H.Luu、Sherwin Ho、Michael J.Lee、Jason Strelzow、Russell R.Reid、Tong-Chuan He

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School of Medicine,Rosalind Franklin University of Medicine and Science,North Chicago,IL 60064,USA

Molecular Oncology Laboratory,Department of Orthopedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL 60637,USA

Ministry of Education Key Laboratory of Diagnostic Medicine,and Department of Clinical Biochemistry,The School of Laboratory Medicine,Chongqing Medical University,Chongqing 400016,China

Department of Orthopedic Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China

Department of Urology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,China

Department of Neurology,The First Dongguan Affiliated Hospital,Guangdong Medical University,Dongguan,Guangdong 523475,China

Department of Clinical Laboratory Medicine,Shanghai Jiaotong University School of Medicine,Shanghai 200000,China

Department of Orthopaedic Surgery,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100730,China

Laboratory of Craniofacial Suture Biology and Development,Department of Surgery Section of Plastic Surgery,The University of Chicago Medical Center,Chicago,IL 60637,USA

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美国国立卫生研究院项目美国国立卫生研究院项目国家自然科学基金2019 Science and Technology Research Plan Project of Chongqing Education Commission(China)2019 Funding for Postdoctoral ResearchChongqing Human Resources and Social Security Bureau,Chongqing,ChinaMedical Scientist Training Program of the National Institutes of HealthUniversity of Chicago Cancer CenterNational Center for Advancing Translational sciences(NCATS)of the National Institutes of HealthMabel Green Myers Research Endowment FundUniversity of Chicago Orthopaedics Alumni Fund

CA226303 to TCHDE030480 to RRR82102696KJQN201900410298T32 GM007281P30CA0145995UL1TR002389

2024

10.1016/j.gendis.2023.04.042

基因与疾病(英文)

基因与疾病(英文)

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年,卷(期)：2024.11(3)
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